Abstract In the United States, opioid use disorder (OUD) and overdose deaths are increasing; yet 80% of opioid users remain out of treatment. Operating in 33 states, syringe exchange programs (SEPs), which provide sterile syringes and other health services to people who inject drugs, are a key venue to reach out-of-treatment opioid users. SEP participants often request referrals for OUD treatment, but structural barriers to care, such as waiting lists or transportation needs, limit engagement in treatment. Therefore structural interventions in health care delivery are necessary to improve engagement in treatment. Buprenorphine maintenance treatment (BMT) is safe and effective, reducing illicit opioid use, HIV risk behaviors, and opioid overdose, and regulations allow for treatment in diverse settings. Therefore, based on the Behavioral Model for Vulnerable Populations and our formative research, we have developed a model to initiate onsite BMT (O-BMT) at SEPs as an innovative and generalizable way to increase BMT engagement. The objectives of this study are to test the effectiveness and safety of O-BMT. In a 24 week randomized controlled trial based in a large urban area with high rates of OUD and HIV, we will recruit 250 out-of-treatment opioid users who utilize SEPs and randomize 1:1 to O- BMT or enhanced referral. Over two weeks, participants in the O-BMT condition will see a buprenorphine provider twice onsite, receive weekly blister packs of medication, and then their care will be transferred to a community health center (CHC) for maintenance BMT. In the control condition, participants will receive enhanced referral to the CHC for BMT. The primary outcome for this study will be engagement in BMT, defined as receiving BMT at 30 days following randomization (effectiveness), and an important secondary outcome will be reduction in HIV risk behaviors (effectiveness). We will also assess buprenorphine diversion (safety) and collect data on programmatic costs and participants? service utilization (cost-effectiveness). The specific aims for this proposal are: 1. To test the effectiveness of initiating onsite buprenorphine treatment (O-BMT) at syringe exchange programs; 2. To test the safety of O-BMT by determining the frequency of buprenorphine diversion; and 3. To determine the cost- effectiveness of O-BMT by comparing costs and health service utilization between study arms.